Humans ; Polycystic Kidney, Autosomal Recessive/genetics*

Objective: To clarify the molecular basis of patients with Bartter syndrome type I and explore the therapeutic effect of trafficking-defective variations by chemical chaperone 4-Phenylbutyric acid(4-PBA). Methods: The clinical characteristics, laboratory findings and genetic data of 3 patients diagnosed with Bartter syndrome type I who were admitted to Department of Nephrology, Children's Hospital of Nanjing Medical University from 2017 to 2018 were retrospectively analyzed. Wild type and variant SLC12A1 gene constructs were transiently overexpressed in HEK293 cells. Western blotting was used to detect the expression levels of Na⁺-K⁺-2Cl^-cotransporter(NKCC2) protein. Immunofluorescent staining was applied to investigate the subcellular localization of NKCC2 protein. In addition, the effect of the chemical chaperone 4-PBA on the expression and localization of the SLC12A1 gene variants was investigated. Unpaired t test was used for statistical analysis of 4-PBA treatment. Results: All the 3 patients (2 males and 1 female), aged 3.0, 4.0 and 1.2 years, respectively. All patients had antenatal onset with polyhydramnios and were born prematurely. After birth, all patients presented with hypochlorine alkalosis accompanied by hypokalemia and hyponatremia. Sequencing analysis revealed that the 3 patients were homozygotes or compound heterozygotes for variants in the SLC12A1 gene. In HEK293 cells, the surface expression of NKCC2 in 3 variants (p.L463S, p.L479V, p.507-510del) are all lower than in wild type (0.718±0.039, 0.287±0.081, 0.025±0.156 vs. 1.001±0.028, t=5.92, 8.35, 30.49, all P<0.01). Moreover, the total protein expression of p.L479V and p.507-510del group were all lower than that in wild type group (0.630±0.032, 0.043±0.003 vs. 1.000±0.111, t=3.21, 8.65, all P<0.05). 4-PBA treatment increased the mature protein expression level of the p.L463S and p. L479V group in 4-PBA treatment group are all higher than the untreated group (0.459±0.018 vs. 1.123±0.024, 0.053±0.012 vs. 1.256±0.037, t=2.75, 18.35, all P<0.05). Cytoplasmic retention of the L479V and 507-510del variants were observed by immunofluorescent staining. 4-PBA treatment could rescue a number of NKCC2 L479V variants to the membrane. Conclusions: The 3 SLC12A1 variants cause expression or subcellular localization defects of the protein. The findings that plasma membrane expression and activity can be rescued by 4PBA might help to develop novel therapeutic strategy for Bartter syndrome type Ⅰ.
Bartter Syndrome/genetics* ; Child, Preschool ; Female ; HEK293 Cells ; Homozygote ; Humans ; Infant ; Male ; Pregnancy ; Retrospective Studies ; Solute Carrier Family 12, Member 1/genetics*

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.
Tibet ; Medicine, Tibetan Traditional ; Quality Control ; Pharmaceutical Research ; Drug Industry

OBJECTIVES: To develop the birth weight curves of the Chinese Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, as well as the birth weight means of full-term neonates of 14 Chinese ethnic groups. METHODS: The live singleton neonates who were born in 11 maternal and child health care hospitals from 11 cities of China between January 2017 and December 2020 were classified according to the mother's ethnic group. Birth weight means were calculated for the full-term neonates of each ethnic group. For the Han and Zhuang singleton neonates with a large sample size, the Lambda-Mu-Sigma (LMS) method was used to establish the birth weight percentile curves of the Han and Zhuang singleton neonates with different gestational ages. RESULTS: A total of 105 365 live singleton neonates were included, among whom the Han neonates had the highest number of 84 851 (26-41 weeks of gestation), followed by the Zhuang neonates (12 803 neonates with a gestational age of 28-41 weeks). The neonates of the other Chinese ethnic groups enrolled were live full-term singleton neonates, with a sample size of more than 100 neonates for each ethnic group. The 3rd-97th percentile curves of birth weight were established for the Han singleton neonates with a gestational age of 26-41 weeks and the Zhuang singleton neonates with a gestational age of 28-41 weeks. The birth weight curves of the Han singleton neonates at each gestational age were higher than those of the Zhuang singleton neonates. Birth weight means (3 199-3 499 g) and standard deviations were determined for 14 Chinese ethnic groups, i.e., Li, Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. The Li ethnic group had the lowest birth weight, followed by the Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. CONCLUSIONS The 3rd-97th percentile curves of birth weight are developed for the Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, and birth weight means are determined for the full-term neonates of 14 Chinese ethnic groups in 11 cities of China, which provides a reference for evaluating the intrauterine growth of neonates in these ethnic groups.
Infant, Newborn ; Male ; Child ; Humans ; Infant ; Birth Weight ; Ethnicity ; Cities ; Gestational Age ; China

Objective To understand the density, populations and habitats of malaria vector Anopheles in Guizhou Province from 2005 to 2019, so as to provide the evidence for formulating the countermeasures to tackle the risk of local transmission of imported malaria in the province. Methods The malaria vector Anopheles density and populations were monitored using human bait trapping and light trapping techniques in Guizhou Province from 2005 to 2019, and all captured Anopheles was morphologically identified and counted. In addition, the distribution of Anopheles habitats was investigated. Results During the period from 2005 through 2019, the malaria vector Anopheles density increased from early June in Guizhou Province, peaked on early July and then declined, which appeared a single peak. The greatest Anopheles density was seen on early August, 2018 [57.34 mosquitoes/(person-night)], and the lowest density was found on late October, 2009 [1.29 mosquitoes/(person-night)]. The annual mean Anopheles density slowly reduced from 17.91 mosquitoes/(person-night) in 2005 to 12.34 mosquitoes/(person-night) in 2012, with a 38.02% reduction (χ²_trend = 115.04, P < 0.01), while the annual mean Anopheles density showed a tendency towards a rise from 2017 to 2019 (χ²_trend = 420.00, P < 0.01). The malaria vector Anopheles was captured during the period between 19 : 00 and 7 : 00 of the next day in Guizhou Province from 2017 to 2019, with the overall density appearing a tendency towards a rise followed by a decline, and the Anopheles activity was highly frequent during the period between 19 : 00 and 21 : 00. The malaria vector Anopheles was monitored for 938 times using the light trapping method in Guizhou Province from 2005 to 2019, and a total of 52 781 Anopheles mosquitoes were captured, including 49 705 An. sinensis, 804 An. minimus, 238 An. anthropophagus, and 2 034 other Anopheles mosquitoes, with a significant difference seen in the Anopheles composition (χ² = 165.68, P < 0.01). From 2017 to 2019, a total of 24 557 Anopheles mosquitoes were captured in human housings, outdoors and livestock housings in Guizhou Province, with 67.65% captured in livestock housings and 12.01% in human housings, and there was a significant difference in the number of Anopheles mosquitoes captured from the three types of habitats (χ² = 55.04, P < 0.01). An. sinensis, An. minimus and An. anthropophagus were captured form all three types of habitats, in which 98.07% was An. sinensis, and 0.09% was An. anthropophagus. Conclusions The population structure of malaria vector Anopheles has changed in historically malaria-endemic areas of Guizhou Province, and An. sinensis has replaced An. minimus and An. anthropophagus to become the predominant malaria vector. The malaria vector Anopheles density has shown a tendency towards a rise in Guizhou Province during the recent years, and there have been a rise in the type and number of Anopheles mosquitoes, leading to a potential risk of local transmission of imported malaria. Long-term, persistent and extensive surveillance of malaria vectors is recommended in Guizhou Province.

【Objective】To investigate the value of medical exome sequencing in copy number variation detection in genetic diseases. 【Methods】 Here we tested two separated cases. There are no similar symptoms except intelligent disability between the cases. Fragile X syndrome，G-banding，chromosome microarray and medical exome sequencing were sequenced tested for the two cases and their parents. 【Results】We found the copy number variants in both of the patients from the two families，which distributed from 11.4 kb to 13.03 Mb in size. The copy number variants were all verified by other technologies. 【Conclusion】 medical exome sequencing is useful for the detection of copy number variation in genetic diseases，although the value still need more verification.

Objective:To observe the effect of Suanzaoren Tang on hippocampal neuroinflammation in APP/PS1 mice and to explore its possible mechanism of neuroprotection. Method:The mice were randomly divided into blank group, model group, donepezil group(0.92 mg·kg^-1), Suanzaoren Tang low and high-dose groups(12.96,25.92 g·kg^-1). After 30 days of continuous administration in each group, pathological changes of dentate gyrus (DG) in hippocampus of mice in each group were observed by Nissl staining.The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum of each group were detected by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of TNF-α and IL-1β in hippocampus of each group. The expression levels of glial fibrillary acidic protein (GFAP) and ionic calcium binding protein 1 (IBA1) in hippocampus of each group were detected by immunohistochemical staining (ICH) and Western blot. Result:Compared with blank group, the granule cells in DG region were unevenly arranged in model group, with obvious cell loss, and the nissl bodies in some neurons disappeared or condensed, serum TNF-α and IL-1β content significantly increased (P<0.01), mice hippocampus of TNF-α and IL-1β mRNA expression quantity significantly increased (P<0.01), levels of GFAP and IBA1 in the hippocampal DG region were significantly up-regulated (P<0.01). Compared with model group,the granule cells in the hippocampal DG region were slightly aligned in donepezil group, Suanzaoren Tang low and high-dose groups, neuron loss of ease, and intracellular austenite disappear or pyknotic conditions improve,the expressions levels of TNF-α and IL-1β in the serum were decreased(P<0.05,P<0.01),the expression levels of TNF-α and IL-1β mRNA in the hippocampus were decreased(P<0.05,P<0.01), protein expression levels of GFAP and IBA1 in the hippocampal DG region were decreased(P<0.05,P<0.01). Conclusion:Suanzaoren Tang can improve neuronal loss in APP/PS1 double transgenic mice, and its mechanism may be related to the regulation of hippocampal neuroinflammation in mice.

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min•1.73 m, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min•1.73 m, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min•1.73 m per year. CONCLUSION Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).
Adult ; Disease Progression ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; drug effects ; Humans ; Kidney Diseases ; drug therapy ; physiopathology ; Male ; Middle Aged ; Outcome Assessment (Health Care)

BackgroundStandard automated perimetry does not sufficiently detect early open-angle glaucoma (OAG) in the clinic. New visual function tests for early glaucoma damage are therefore needed. The present study evaluated whether an isolated-check visual evoked potential (icVEP) could be used to detect visual function abnormalities in early-stage OAG and to explore potential related factors.

MethodsThis was a cross-sectional study. Thirty-seven OAG patients with early-stage visual field loss (mean deviation ≥ -6.00 dB) detected by the Humphrey Field Analyzer (30-2 SITA program) and 26 controls were included in this study. Optical coherence tomography (OCT) was used to detect retinal nerve fiber layer (RNFL) defects. The icVEP preferentially evaluates the magnocellular-ON pathway. VEPs were recorded and signal-to-noise ratios (SNRs) were derived based on multivariate analysis. Eyes that yielded an SNR ≤1 were considered abnormal. Receiver operating characteristic (ROC) curve analysis was used to estimate the accuracy of group classification. Correlations between SNRs and related factors were analyzed.

ResultsBased on an SNR criterion of 1, the icVEP had a sensitivity of 62.2% and a specificity of 92.3% for diagnosing early-stage OAG with 74.6% classification accuracy. The ROC curve analysis, however, suggested that an SNR criterion of 0.93 would produce the highest classification accuracy (77.3%). Both RNFL thinning in the temporal superior quadrant on OCT and number of abnormal test points in the central 11° visual field (pattern deviation, P < 0.5%) significantly correlated with the SNR (P < 0.05).

ConclusionsThe icVEP detected visual function abnormalities in approximately 3/5 of eyes with early-stage OAG with greater than 90% specificity. SNR correlated with both a decrease in RNFL thickness and severity of central visual field loss.

Hospital information platform had its present situation and problems in integration introduced, and its construction contents and mode were described. The solutions from some famous foreign companies such as Orion and InterSystems were discussed from the aspects of core architecture and technical characteristics.It's pointed out that urgent requirements and the benefit balance between different companies had to be emphasized so as to develop a platform for data sharing and exchange as well as information export.